Existing drugs could treat gastric cancer

Washington: Certain drugs currently used to treat breast, ovarian and pancreatic cancers, could also be used to treat some gastric cancers, researchers have found.

Gastric cancer, otherwise known as stomach cancer, does not respond well to existing treatments and it is currently the third leading cause of cancer death in the world, after lung and liver cancer.

Researchers have discovered that certain drugs, currently used to treat breast, ovarian and pancreatic cancers, could also be used to treat certain gastric cancers with a particular pattern of mutations (genomic molecular fingerprint).

Recent research has shown that a specific genomic molecular fingerprint, called signature 3, is associated with cells that have defective DNA repair mechanisms, for example due to faulty BRCA1 or BRCA2 genes which are linked with breast cancer.

Cancer cells harbouring signature 3 have defects that stop them from efficiently repairing damage to their DNA.

Due to their inability to repair DNA damage, these cells become vulnerable to platinum drugs and PARP inhibitor drugs, both of which attack DNA, causing it to break.

Since the DNA damage cannot then be repaired, the cancer cell dies.

Signature 3 could therefore predict which cancers would be likely to respond to particular drug therapies.

“We analysed the cancer genomes of 10,250 patients, performing a large-scale computational screen across 36 different types of tumours, looking for the pattern of Signature 3 in each sample,” said corresponding author Ludmil Alexandrov of the Los Alamos National Laboratory in US.

“Not only did we confirm the presence of signature 3 in a significant percentage of breast, ovarian, and pancreatic cancers, we also found this molecular fingerprint in approximately 10 per cent of stomach cancers,” Alexandrov said.

“This subset of stomach cancer is likely to have a defective DNA break-repair mechanism, and could therefore be susceptible to existing treatments such as platinum drugs or PARP inhibitor drugs,” he said.

In addition to discovering the pattern of signature 3 in gastric cancer, the study quantified its occurrence in other cancer types.

It showed that 30 per cent of ovarian, 27 per cent of breast and 8 per cent of pancreatic cancers exhibit this molecular fingerprint, a higher percentage than originally thought.

Previous research using whole genome sequencing data showed that pancreatic cancers harbouring the signature 3 fingerprint responded very well to platinum therapy.

This suggests that the presence of signature 3 could be used as a biomarker to guide targeted therapy for not just some gastric cancers, but also for breast, ovarian and pancreatic cancers.